Gait Disorders in Old Age, Muscle Weakness, Sarcopenia
Conditions
Keywords
Sarcopenia, Sarcopenic Obesity, 6-minute walking distance, 400 meters walking test, BIO101, Short Physical Performance Battery, Appendicular lean mass
Brief summary
The main objective of the study is to evaluate the effect of two daily doses of BIO101 versus placebo on mobility function as measured by gait speed using the 400MW test. The absolute change from baseline in meters/second observed in each treatment group at 6 Month was compared to the placebo group. Due to the Covid pandemic \>50% of data at endpoint was missing, which may have affected the ability of the study to deliver the expected results. Additionally, although the planned duration of treatment was 6 months, it was extended up to 9 months for some participants as a result of the pandemic.
Detailed description
The aim of this phase 2 double-blind, placebo-controlled, randomized interventional clinical trial (SARA-INT) is to evaluate the safety and efficacy of BIO-101 175 mg b.i.d. and 350 mg b.i.d. 9 months oral administration to participants suffering from age-related sarcopenia, including sarcopenic obesity, aged ≥65 years and at risk of mobility disability. There are 3-arms (2 doses versus placebo). This comparative clinical trial evaluated the effects up to 9 month treatment duration, based on the hypothesis that physical function of sarcopenic, older participants with an initial degree of mobility disability (SPPB) may be improved by BIO101. Included participants were randomized in a 1:1:1 ratio, to one of the 3 arms of treatment in a blinded manner. The randomization was stratified by gender and by center. Based on absence of long-term toxicology data, the investigational drug exposure was initially capped at 6 months.
Interventions
DRUGBIO101
Oral capsules
DRUGPlacebo
Oral capsules
Sponsors
Biophytis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Each treatment kit showed a preprinted kit number affixed on the primary, secondary and tertiary container. The kit number was assigned via the eCRF after a participant is qualified and was randomized. Neither the Investigator and his staff, nor the Sponsor was aware of the treatment that corresponds to the kit number. The assigned treatment cannot be retrieved from the system, unless a specific unblinding procedure was engaged by the investigator when this was judged necessary by the responsible physician of the investigator center in the context of a severe or serious adverse event.
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Male or female, aged ≥ 65 years and living in the community, reporting loss of physical function over the last 6-12 months 4. Short Physical Performance Battery (SPPB) score ≤ 8 5. ALM/BMI \< 0.789 in men and 0.512 in women, or ALM \< 19.75kg in men and \<15.02kg in women, as measured by DEXA scan 6. Ability to take oral medication and be willing to adhere to the study intervention regimen. 7. Agreement to adhere to Lifestyle Considerations throughout study duration 8. In the US, women and members of minority groups must be included in accordance with the NIH Policy on Inclusion of Women and Minorities as Participants In Research Involving Human participants.
Exclusion criteria
1. Current use of anabolic drugs (e.g. testosterone); current use of Erythropoietin; current use of corticosteroid agents (except local administration route, like eye drops or dermatologic formulations) 2. Non-menopaused women (however ongoing replacement hormonal treatment is not an exclusion criterion) 3. Known allergic reactions to components of the investigational drug. 4. Treatment with another investigational drug or other intervention within three months 5. Unable to understand and perform the functional tests, as judged by the Investigator 6. Inability to perform the 400MW test within 15 minutes 7. Clinical conditions: 1. Current diagnosis of major psychiatric disorders. 2. Alcohol abuse or dependence 3. Severe arthritis 4. Cancer requiring active treatment (cancer treated with chemotherapy, or radiotherapy and currently on remission is not an exclusion criterion) 5. Lung disease requiring regular use of supplemental oxygen 6. Inflammatory conditions requiring regular use of oral or parenteral corticosteroid agents 7. Severe cardiovascular disease (including New York Heart Association \[NYHA\] class III or IV congestive heart failure, clinically significant valvular disease, history of cardiac arrest, presence of an implantable defibrillator, or uncontrolled angina) 8. Parkinson's disease or other progressive neurological disorder 9. Renal disease requiring dialysis, or known renal insufficiency (moderate or severe reduction in GFR≤30 ml/min/1.73 m2) 10. Chest pain, severe shortness of breath, or occurrence of other safety concerns during the baseline functional tests 400-meter walk test or 6MWT 11. History or active signs or symptoms of gallbladder/biliary disease (e.g. previous episodes of cholestasis/biliary tract obstruction, cholelithiasis, cholecystitis, etc.). Of note, history of cholecystectomy and no active biliary signs or symptoms, is not an exclusion criterion. 8. Current physical/rehabilitation therapy (except for passive physical therapy. However, this should not be initiated the week before an evaluation visit and once started, it should be maintained over the study duration).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test | Baseline and 6 Months | Gait speed was measured using the 400 MW test, which measured how long it took the participant to walk a distance of 400 meters. Missing data imputed using adjusted Bayesian Multiple Imputation (MI) methods for Non-Completers who failed to perform the Test feasibility and Multiple Imputation for participants who without data on on-Site visit. Data up to 9 months was used where 6 months data were unavailable for participants enrolled during the COVID-19 pandemic. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 6 Months in Handgrip Strength Test | Baseline and 6 Months | Handgrip strength was a commonly used measure of upper body skeletal muscle function and had been widely used as a general indicator of frailty with predictive validity for both mortality and functional limitations. Participants were instructed to stand upright and with the dynamometer beside them but not against their body. Strength was measured three times for both hands. The highest value of all 3 attempts was kept for further analysis. Grip strength was measured in the dominant hand using a hydraulic grip strength dynamometer. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic. |
| Change From Baseline to 6 Months in Appendicular Lean Body Mass (ALM) Based on Dual-energy X-ray Absorptiometry (DEXA) Measurements | Baseline and 6 Months | DEXA scans provided accurate measurements of body composition, recording fat and lean mass distribution throughout the entire body. Foundation of National Health Institute (FNIH) project report recommended ALM alone was used to measure gender-specific low muscle mass. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic. |
| Rate of Response for Completing 400 MW Test After 6 Months | Baseline and 6 Months | A responder was defined as an improvement (increase) of 0.1 m/s or more in 400MW gait speed test compared to baseline. A non-responder was defined as a participant that was not a responder. Participants with a missing value at the visit and/or missing baseline value were considered as non-responders. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic. |
| Change From Baseline to 6 Months in Muscle Strength Based on Knee Extension | Baseline and 6 Months | Isometric knee extension torque was measured with a knee extension dynamometer chair. The participants were positioned in an upright position, with straps to affix the hips to the chair and the ankle to a force or torque transducer at the knee angle of 90°. Lever arm length was recorded as the distance between the knee axis of rotation and the middle of the pad. Knee extension was measured using the maximum peak torque measurement Newton meter (Nm) for 60°/s, 90°/s and 180°/s for the tested leg (either right or left). The Knee extension torque was obtained either directly or by multiplying recorded peak force with the lever arm length. The assay with the highest torque output was taken for analyses. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic. |
| Change From Baseline to 6 Months in Time for Five Chair Stands as Part of the Short Physical Performance Battery (SPPB) Assessment | Baseline and 6 Months | The SPPB was a series of tests designed to examine physical movements. The chair stands tests involved standing from a chair a number of times to test leg strength. Each performance measures were assigned a score ranging from 0 to 4, with 4 indicating the highest level of performance and 0 the inability to complete the test. The time to complete the task was recorded. The time required to perform five chair stands was scored as follows: ≥ 16.70 sec = 1; 13.70 to 16.69 sec = 2; 11.20 to 13.69 sec = 3; ≤ 11.19 = 4. A score of 0 was assigned to participants unable to perform the task. A summary score ranging from 0 (worst performers) to 12 (best performers) was calculated by adding sub scores from the chair stands test. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic. |
| Change From Baseline to 6 Months in Short Form-36 (SF-36) 10 Item Physical Function Domain (PF-10) Sub-score | Baseline and 6 Months | The Physical Function Domain (PF-10) of the SF-36 assesses an individual's perceived physical functioning and limitations in various activities. It consists of ten items that ask about a person's ability to perform different physical activities and tasks. Scores on the PF-10 range from 0 to 100 where 100 indicates no physical limitations. Missing data imputed using adjusted Bayesian MI methods. Data up to 9 month was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic. |
| Change From Baseline to 6 Months in Pepper Assessment Tool for Disability (PAT-D) for Obese Participants | Baseline and 6 Months | The PAT-D was a disability questionnaire which asked respondents how much difficulty they had with a range of activities with functioning. PAT-D scores range from 1 (worst) to 5 (best). Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic. |
| Change From Baseline to 6 Months in SPPB Total Score | Baseline and 6 Months | The SPPB was a series of tests designed to examine physical movements. Results of the SPPB included total gait speed score, total balance test score, and total chair stand score. The first tests examined balance (without the assistance of a cane or walker) with the feet in three different orientations, the second test examined gait speed, and the third tests involved standing from a Chair a number of times to test leg strength. A score of 0 was assigned to participants unable to perform the task. A summary score ranging from 0 (worst performers) to 12 (best performers) was calculated by adding sub scores from the walking speed, chair stands and balance tests. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic. |
| Change From Baseline to 6 Months in Sarcopenia Quality of Life (SarQoL) Auto-Evaluation Questionnaire | Baseline and 6 Months | The SarQoL was a sarcopenia-specific, self-administered, quality of life questionnaire designed for community-dwelling elderly study participants aged 65 years and older. The questionnaire contained 22 questions, which took approximately 10 minutes to complete. The questionnaire covered 7 domains: physical and mental health; locomotion; body composition; functionality; activities of daily living; leisure activities; and fears. Most questions are answered on a 4 point Likert scale. The total scoring of the SarQoL questionnaire ranges from 0 (worst imaginable health) to 100 (best imaginable health). A higher score reflected a higher quality of life. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic. |
| Change From Baseline to 6 Months in Stair Climb Power Test (SCPT) | Baseline and 6 Months | The SCPT measured the ability to ascend and descend stairs and tests lower body strength and balance and measures time (in seconds) taken to ascend and descend a flight of stairs (10 steps with a 20 cm step height; a handrail was recommended). Step heights should have been suitable (between 16 and 20 cm). Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic. |
| Change From Baseline to 6 Months in Distance in the 6-Minute Walk Test (6MWT) | Baseline and 6 Months | The 6MWT was a test for functional exercise capacity and involved measuring the distance a participant could cover within the allotted time of 6 minutes. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic. |
Countries
Belgium, United States
Participant flow
Recruitment details
Participants were enrolled from 19 centers in the United States and 3 centers in Belgium.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months. | 81 |
| 175mg BIO101 BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months. | 75 |
| 350mg BIO101 BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months. | 76 |
| Total | 232 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 6 | 1 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 | 0 |
| Overall Study | Other | 0 | 2 | 2 |
| Overall Study | PI Decision | 1 | 0 | 0 |
| Overall Study | Withdraw due to the COVID-19 outbreak | 1 | 0 | 1 |
| Overall Study | Withdrew consent | 4 | 2 | 2 |
Baseline characteristics
| Characteristic | 350mg BIO101 | Placebo | 175mg BIO101 | Total |
|---|---|---|---|---|
| Age, Continuous | 76.3 Years STANDARD_DEVIATION 6.38 | 75.5 Years STANDARD_DEVIATION 7.12 | 76.2 Years STANDARD_DEVIATION 7.1 | 76.0 Years STANDARD_DEVIATION 6.86 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 14 Participants | 13 Participants | 13 Participants | 40 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 7 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 61 Participants | 65 Participants | 55 Participants | 181 Participants |
| Region of Enrollment Belgium | 7 participants | 7 participants | 6 participants | 20 participants |
| Region of Enrollment United States | 69 participants | 74 participants | 69 participants | 212 participants |
| Sex: Female, Male Female | 38 Participants | 44 Participants | 37 Participants | 119 Participants |
| Sex: Female, Male Male | 38 Participants | 37 Participants | 38 Participants | 113 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 81 | 0 / 75 | 1 / 74 |
| other Total, other adverse events | 48 / 81 | 45 / 75 | 38 / 74 |
| serious Total, serious adverse events | 10 / 81 | 10 / 75 | 4 / 74 |
Outcome results
Primary
Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test
Gait speed was measured using the 400 MW test, which measured how long it took the participant to walk a distance of 400 meters. Missing data imputed using adjusted Bayesian Multiple Imputation (MI) methods for Non-Completers who failed to perform the Test feasibility and Multiple Imputation for participants who without data on on-Site visit. Data up to 9 months was used where 6 months data were unavailable for participants enrolled during the COVID-19 pandemic.
Time frame: Baseline and 6 Months
Population: Full Analysis Set: The Full Analysis Set (FAS) population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. Participants with data available were included.~One participant randomized but not treated with 175 mg BIO101.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test | Gait Speed Based on Adjusted Bayesian Imputation | -0.2886 Meter/Second (m/s) |
| Placebo | Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test | Gait Speed based on Mixed Effect Model | 0.0093 Meter/Second (m/s) |
| Placebo | Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test | MI + Adjusted Bayesian Imputation | -0.0188 Meter/Second (m/s) |
| 175mg BIO101 | Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test | Gait Speed Based on Adjusted Bayesian Imputation | -0.2543 Meter/Second (m/s) |
| 175mg BIO101 | Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test | Gait Speed based on Mixed Effect Model | 0.0457 Meter/Second (m/s) |
| 175mg BIO101 | Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test | MI + Adjusted Bayesian Imputation | -0.0066 Meter/Second (m/s) |
| 350mg BIO101 | Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test | Gait Speed based on Mixed Effect Model | 0.0478 Meter/Second (m/s) |
| 350mg BIO101 | Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test | MI + Adjusted Bayesian Imputation | 0.0500 Meter/Second (m/s) |
| 350mg BIO101 | Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test | Gait Speed Based on Adjusted Bayesian Imputation | -0.2014 Meter/Second (m/s) |
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic.p-value: 0.2437Mixed Models Analysis
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemicp-value: 0.2Mixed Models Analysis
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic based on adjusted Bayesian Imputationp-value: 0.324Adjusted Bayesian Imputation
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic based on adjusted Bayesian Imputationp-value: 0.5123Adjusted Bayesian Imputation
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic based on MI and Adjusted Bayesian Imputationp-value: 0.692Mixed Models Analysis
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic based on MI and Adjusted Bayesian Imputationp-value: 0.085Mixed Models Analysis
Secondary
Change From Baseline to 6 Months in Appendicular Lean Body Mass (ALM) Based on Dual-energy X-ray Absorptiometry (DEXA) Measurements
DEXA scans provided accurate measurements of body composition, recording fat and lean mass distribution throughout the entire body. Foundation of National Health Institute (FNIH) project report recommended ALM alone was used to measure gender-specific low muscle mass. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.
Time frame: Baseline and 6 Months
Population: Full Analysis Set: Population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. Participants with data available were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to 6 Months in Appendicular Lean Body Mass (ALM) Based on Dual-energy X-ray Absorptiometry (DEXA) Measurements | -0.276 Kg |
| 175mg BIO101 | Change From Baseline to 6 Months in Appendicular Lean Body Mass (ALM) Based on Dual-energy X-ray Absorptiometry (DEXA) Measurements | -0.283 Kg |
| 350mg BIO101 | Change From Baseline to 6 Months in Appendicular Lean Body Mass (ALM) Based on Dual-energy X-ray Absorptiometry (DEXA) Measurements | 0.068 Kg |
p-value: 0.9859ANCOVA
Comparison: Statistical Analysis of Change from Baseline in ALMp-value: 0.404ANCOVA
Secondary
Change From Baseline to 6 Months in Distance in the 6-Minute Walk Test (6MWT)
The 6MWT was a test for functional exercise capacity and involved measuring the distance a participant could cover within the allotted time of 6 minutes. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.
Time frame: Baseline and 6 Months
Population: Full Analysis Set: Population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. Participants with data available were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to 6 Months in Distance in the 6-Minute Walk Test (6MWT) | -9.879 Meters |
| 175mg BIO101 | Change From Baseline to 6 Months in Distance in the 6-Minute Walk Test (6MWT) | -7.166 Meters |
| 350mg BIO101 | Change From Baseline to 6 Months in Distance in the 6-Minute Walk Test (6MWT) | 15.728 Meters |
p-value: 0.8824ANCOVA
p-value: 0.1578ANCOVA
Secondary
Change From Baseline to 6 Months in Handgrip Strength Test
Handgrip strength was a commonly used measure of upper body skeletal muscle function and had been widely used as a general indicator of frailty with predictive validity for both mortality and functional limitations. Participants were instructed to stand upright and with the dynamometer beside them but not against their body. Strength was measured three times for both hands. The highest value of all 3 attempts was kept for further analysis. Grip strength was measured in the dominant hand using a hydraulic grip strength dynamometer. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.
Time frame: Baseline and 6 Months
Population: Full Analysis Set: Population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. Participants with data available were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline to 6 Months in Handgrip Strength Test | Handgrip strength Test at Month 6 (dominant hand) | -0.709 kilograms (Kg) |
| Placebo | Change From Baseline to 6 Months in Handgrip Strength Test | Handgrip strength test at month 6 (Left hand) | -0.860 kilograms (Kg) |
| Placebo | Change From Baseline to 6 Months in Handgrip Strength Test | Handgrip strength test at month 6 (Right hand) | -0.842 kilograms (Kg) |
| Placebo | Change From Baseline to 6 Months in Handgrip Strength Test | Based on Multiple Imputation (dominant hand) | 0.145 kilograms (Kg) |
| 175mg BIO101 | Change From Baseline to 6 Months in Handgrip Strength Test | Based on Multiple Imputation (dominant hand) | 0.297 kilograms (Kg) |
| 175mg BIO101 | Change From Baseline to 6 Months in Handgrip Strength Test | Handgrip strength Test at Month 6 (dominant hand) | -1.601 kilograms (Kg) |
| 175mg BIO101 | Change From Baseline to 6 Months in Handgrip Strength Test | Handgrip strength test at month 6 (Right hand) | -1.664 kilograms (Kg) |
| 175mg BIO101 | Change From Baseline to 6 Months in Handgrip Strength Test | Handgrip strength test at month 6 (Left hand) | -1.597 kilograms (Kg) |
| 350mg BIO101 | Change From Baseline to 6 Months in Handgrip Strength Test | Based on Multiple Imputation (dominant hand) | 0.663 kilograms (Kg) |
| 350mg BIO101 | Change From Baseline to 6 Months in Handgrip Strength Test | Handgrip strength test at month 6 (Left hand) | 0.319 kilograms (Kg) |
| 350mg BIO101 | Change From Baseline to 6 Months in Handgrip Strength Test | Handgrip strength test at month 6 (Right hand) | 0.865 kilograms (Kg) |
| 350mg BIO101 | Change From Baseline to 6 Months in Handgrip Strength Test | Handgrip strength Test at Month 6 (dominant hand) | 0.590 kilograms (Kg) |
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic in Handgrip Strength Test (dominant hand)p-value: 0.52ANCOVA
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic in Handgrip Strength Test (dominant hand)p-value: 0.3577ANCOVA
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic in Handgrip Strength Test at Month 6 Based on Multiple Imputation (dominant hand)p-value: 0.9237ANCOVA
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic in Handgrip Strength Test at Month 6 Based on Multiple Imputation (dominant hand)p-value: 0.7629ANCOVA
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic in Change from Baseline in Handgrip Strength Test (left hand)p-value: 0.5695ANCOVA
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic in Handgrip Strength Test (Left hand)p-value: 0.3523ANCOVA
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic in Handgrip Strength Test (Right hand)p-value: 0.5652ANCOVA
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic in Handgrip Strength Test (Right hand)p-value: 0.2472ANCOVA
Secondary
Change From Baseline to 6 Months in Muscle Strength Based on Knee Extension
Isometric knee extension torque was measured with a knee extension dynamometer chair. The participants were positioned in an upright position, with straps to affix the hips to the chair and the ankle to a force or torque transducer at the knee angle of 90°. Lever arm length was recorded as the distance between the knee axis of rotation and the middle of the pad. Knee extension was measured using the maximum peak torque measurement Newton meter (Nm) for 60°/s, 90°/s and 180°/s for the tested leg (either right or left). The Knee extension torque was obtained either directly or by multiplying recorded peak force with the lever arm length. The assay with the highest torque output was taken for analyses. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.
Time frame: Baseline and 6 Months
Population: Full Analysis Set: Population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. This data represents Knee Extension of Highest Reading from all Degrees. Participants with data available were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to 6 Months in Muscle Strength Based on Knee Extension | 0.484 Newton meter (Nm) |
| 175mg BIO101 | Change From Baseline to 6 Months in Muscle Strength Based on Knee Extension | -1.092 Newton meter (Nm) |
| 350mg BIO101 | Change From Baseline to 6 Months in Muscle Strength Based on Knee Extension | -4.515 Newton meter (Nm) |
p-value: 0.8917ANCOVA
p-value: 0.631795% CI: [-26.777, 16.778]ANCOVA
Secondary
Change From Baseline to 6 Months in Pepper Assessment Tool for Disability (PAT-D) for Obese Participants
The PAT-D was a disability questionnaire which asked respondents how much difficulty they had with a range of activities with functioning. PAT-D scores range from 1 (worst) to 5 (best). Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.
Time frame: Baseline and 6 Months
Population: Full Analysis Set: Population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. Participants with data available were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to 6 Months in Pepper Assessment Tool for Disability (PAT-D) for Obese Participants | -0.27 score on a scale |
| 175mg BIO101 | Change From Baseline to 6 Months in Pepper Assessment Tool for Disability (PAT-D) for Obese Participants | -0.08 score on a scale |
| 350mg BIO101 | Change From Baseline to 6 Months in Pepper Assessment Tool for Disability (PAT-D) for Obese Participants | -0.17 score on a scale |
p-value: 0.0511ANCOVA
p-value: 0.2771ANCOVA
Secondary
Change From Baseline to 6 Months in Sarcopenia Quality of Life (SarQoL) Auto-Evaluation Questionnaire
The SarQoL was a sarcopenia-specific, self-administered, quality of life questionnaire designed for community-dwelling elderly study participants aged 65 years and older. The questionnaire contained 22 questions, which took approximately 10 minutes to complete. The questionnaire covered 7 domains: physical and mental health; locomotion; body composition; functionality; activities of daily living; leisure activities; and fears. Most questions are answered on a 4 point Likert scale. The total scoring of the SarQoL questionnaire ranges from 0 (worst imaginable health) to 100 (best imaginable health). A higher score reflected a higher quality of life. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.
Time frame: Baseline and 6 Months
Population: Full Analysis Set: Population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. This data represents overall disability score. Participants with data available were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to 6 Months in Sarcopenia Quality of Life (SarQoL) Auto-Evaluation Questionnaire | 8.05 score on a scale |
| 175mg BIO101 | Change From Baseline to 6 Months in Sarcopenia Quality of Life (SarQoL) Auto-Evaluation Questionnaire | 5.60 score on a scale |
| 350mg BIO101 | Change From Baseline to 6 Months in Sarcopenia Quality of Life (SarQoL) Auto-Evaluation Questionnaire | 5.83 score on a scale |
p-value: 0.2312Mixed Models Analysis
p-value: 0.2701Mixed Models Analysis
Secondary
Change From Baseline to 6 Months in Short Form-36 (SF-36) 10 Item Physical Function Domain (PF-10) Sub-score
The Physical Function Domain (PF-10) of the SF-36 assesses an individual's perceived physical functioning and limitations in various activities. It consists of ten items that ask about a person's ability to perform different physical activities and tasks. Scores on the PF-10 range from 0 to 100 where 100 indicates no physical limitations. Missing data imputed using adjusted Bayesian MI methods. Data up to 9 month was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.
Time frame: Baseline and 6 Months
Population: Full Analysis Set: Population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. Participants with data available were included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline to 6 Months in Short Form-36 (SF-36) 10 Item Physical Function Domain (PF-10) Sub-score | Analysis based on Mixed Effect Model for MMRM | 7.3 score on a scale |
| Placebo | Change From Baseline to 6 Months in Short Form-36 (SF-36) 10 Item Physical Function Domain (PF-10) Sub-score | Based on Adjusted Bayesian Imputation | 1.4 score on a scale |
| 175mg BIO101 | Change From Baseline to 6 Months in Short Form-36 (SF-36) 10 Item Physical Function Domain (PF-10) Sub-score | Analysis based on Mixed Effect Model for MMRM | 7.1 score on a scale |
| 175mg BIO101 | Change From Baseline to 6 Months in Short Form-36 (SF-36) 10 Item Physical Function Domain (PF-10) Sub-score | Based on Adjusted Bayesian Imputation | 4.0 score on a scale |
| 350mg BIO101 | Change From Baseline to 6 Months in Short Form-36 (SF-36) 10 Item Physical Function Domain (PF-10) Sub-score | Analysis based on Mixed Effect Model for MMRM | 7.1 score on a scale |
| 350mg BIO101 | Change From Baseline to 6 Months in Short Form-36 (SF-36) 10 Item Physical Function Domain (PF-10) Sub-score | Based on Adjusted Bayesian Imputation | 4.1 score on a scale |
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic in Physical Function Domain (PF-10) Sub-score based on Mixed Model Analysisp-value: 0.9408Mixed Models Analysis
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic in Physical Function Domain (PF-10) Sub-score based on Mixed Model Analysisp-value: 0.9485Mixed Models Analysis
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic in Physical Function Domain (PF-10) Sub-Score Based on Adjusted Bayesian Imputationp-value: 0.9848Mixed Models Analysis
Comparison: Analysis of data collected from baseline to 6 months, or baseline to 9 months due to pandemic in Physical Function Domain (PF-10) Sub-Score Based on Adjusted Bayesian Imputationp-value: 0.5017Mixed Models Analysis
Secondary
Change From Baseline to 6 Months in SPPB Total Score
The SPPB was a series of tests designed to examine physical movements. Results of the SPPB included total gait speed score, total balance test score, and total chair stand score. The first tests examined balance (without the assistance of a cane or walker) with the feet in three different orientations, the second test examined gait speed, and the third tests involved standing from a Chair a number of times to test leg strength. A score of 0 was assigned to participants unable to perform the task. A summary score ranging from 0 (worst performers) to 12 (best performers) was calculated by adding sub scores from the walking speed, chair stands and balance tests. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.
Time frame: Baseline and 6 Months
Population: Full Analysis Set: Population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. Participants with data available were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to 6 Months in SPPB Total Score | 1.1 score on a scale |
| 175mg BIO101 | Change From Baseline to 6 Months in SPPB Total Score | 1.00 score on a scale |
| 350mg BIO101 | Change From Baseline to 6 Months in SPPB Total Score | 0.9 score on a scale |
p-value: 0.8084Mixed Models Analysis
p-value: 0.7266Mixed Models Analysis
Secondary
Change From Baseline to 6 Months in Stair Climb Power Test (SCPT)
The SCPT measured the ability to ascend and descend stairs and tests lower body strength and balance and measures time (in seconds) taken to ascend and descend a flight of stairs (10 steps with a 20 cm step height; a handrail was recommended). Step heights should have been suitable (between 16 and 20 cm). Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.
Time frame: Baseline and 6 Months
Population: Full Analysis Set: Population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. Participants with data available were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to 6 Months in Stair Climb Power Test (SCPT) | 39.9 Seconds |
| 175mg BIO101 | Change From Baseline to 6 Months in Stair Climb Power Test (SCPT) | 32.4 Seconds |
| 350mg BIO101 | Change From Baseline to 6 Months in Stair Climb Power Test (SCPT) | 88.5 Seconds |
p-value: 0.8934ANCOVA
p-value: 0.3526ANCOVA
Secondary
Change From Baseline to 6 Months in Time for Five Chair Stands as Part of the Short Physical Performance Battery (SPPB) Assessment
The SPPB was a series of tests designed to examine physical movements. The chair stands tests involved standing from a chair a number of times to test leg strength. Each performance measures were assigned a score ranging from 0 to 4, with 4 indicating the highest level of performance and 0 the inability to complete the test. The time to complete the task was recorded. The time required to perform five chair stands was scored as follows: ≥ 16.70 sec = 1; 13.70 to 16.69 sec = 2; 11.20 to 13.69 sec = 3; ≤ 11.19 = 4. A score of 0 was assigned to participants unable to perform the task. A summary score ranging from 0 (worst performers) to 12 (best performers) was calculated by adding sub scores from the chair stands test. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.
Time frame: Baseline and 6 Months
Population: Full Analysis Set: Population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. Participants with data available were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline to 6 Months in Time for Five Chair Stands as Part of the Short Physical Performance Battery (SPPB) Assessment | -3.857 Seconds |
| 175mg BIO101 | Change From Baseline to 6 Months in Time for Five Chair Stands as Part of the Short Physical Performance Battery (SPPB) Assessment | -2.572 Seconds |
| 350mg BIO101 | Change From Baseline to 6 Months in Time for Five Chair Stands as Part of the Short Physical Performance Battery (SPPB) Assessment | -1.206 Seconds |
p-value: 0.3762Mixed Models Analysis
p-value: 0.0543Mixed Models Analysis
Secondary
Rate of Response for Completing 400 MW Test After 6 Months
A responder was defined as an improvement (increase) of 0.1 m/s or more in 400MW gait speed test compared to baseline. A non-responder was defined as a participant that was not a responder. Participants with a missing value at the visit and/or missing baseline value were considered as non-responders. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.
Time frame: Baseline and 6 Months
Population: Full Analysis Set: Population consists of randomized participants, excluding participants who failed to take at least one dose of trial medication and had a very early withdrawal (first week after randomization) definitely not related to study medication and lacked any post randomization data. Participants with rate of response for completing 400 MW test were included in the analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Rate of Response for Completing 400 MW Test After 6 Months | Responder | 4 Participants |
| Placebo | Rate of Response for Completing 400 MW Test After 6 Months | Non-responder | 77 Participants |
| 175mg BIO101 | Rate of Response for Completing 400 MW Test After 6 Months | Responder | 9 Participants |
| 175mg BIO101 | Rate of Response for Completing 400 MW Test After 6 Months | Non-responder | 66 Participants |
| 350mg BIO101 | Rate of Response for Completing 400 MW Test After 6 Months | Responder | 11 Participants |
| 350mg BIO101 | Rate of Response for Completing 400 MW Test After 6 Months | Non-responder | 65 Participants |
p-value: 0.1219Regression, Logistic
p-value: 0.052Regression, Logistic